The goal of this project is to evaluate the immunogenicity and efficacy of DNA vaccines in neonatal rhesus macaques. In a collaborative effort with Dr. Harriet Robinson, a vaccine study was designed for neonatal macaques to parallel her vaccine efficacy trial in juvenile/adult monkeys. After a series of inoculations with DNA expression vectors encoding SHIV-vpu+ antigens, no neutralizing antibody responses were seen in any animal, even though anti-Env responses were detectable by an ELISA. Consequently, all animals primed with DNA expression vectors for envelope glycoproteins were boosted twice with recombinant gp160. Some vaccinees developed high levels of neutralizing antibodies. Five months ago, all animals were challenged with 10 50% animal infectious doses (10 AIDS50) of homologous SHIV-vpu+. Six animals were either completely resistant to challenge or had only transient, low numbers of infectious cells. These 6 animals were challenged a second time wit h homolog ous SHIV-vpu+ two months ago. Four of these animals have resisted again, whereas the other 2 have very low levels of virus. We plan to challenge them with pathogenic heterologous SHIV-89.6p. Thus far, we have demonstrated that neonatal macaques can generate protective immunity when vaccinated with a DNA prime/protein boost regimen. FUNDING U.S. Army $225,725 9/30/94 - 9/29/99 PUBLICATIONS None P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center